CN102802627A - 电压门控的钠通道阻滞剂 - Google Patents
电压门控的钠通道阻滞剂 Download PDFInfo
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- CN102802627A CN102802627A CN2011800141112A CN201180014111A CN102802627A CN 102802627 A CN102802627 A CN 102802627A CN 2011800141112 A CN2011800141112 A CN 2011800141112A CN 201180014111 A CN201180014111 A CN 201180014111A CN 102802627 A CN102802627 A CN 102802627A
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- CN
- China
- Prior art keywords
- methyl
- phenyl
- methylethyl
- piperazinyl
- oxy
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 239000000664 voltage gated sodium channel blocking agent Substances 0.000 title abstract description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 337
- 238000000034 method Methods 0.000 claims abstract description 60
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 45
- 208000023504 respiratory system disease Diseases 0.000 claims abstract description 27
- 239000000539 dimer Substances 0.000 claims abstract description 24
- 238000011282 treatment Methods 0.000 claims abstract description 23
- 230000000241 respiratory effect Effects 0.000 claims abstract description 11
- -1 2-{(3S)-3-[{[(1,1-Dimethylethyl)oxy]carbonyl}(methyl)amino]-1-pyrrolidinyl}-3-pyridinecarboxylic acid Chemical compound 0.000 claims description 401
- PZQSQRCNMZGWFT-QXMHVHEDSA-N propan-2-yl (z)-octadec-9-enoate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC(C)C PZQSQRCNMZGWFT-QXMHVHEDSA-N 0.000 claims description 268
- 125000000217 alkyl group Chemical group 0.000 claims description 216
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 208
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 132
- 150000002148 esters Chemical class 0.000 claims description 103
- 150000003839 salts Chemical class 0.000 claims description 96
- 125000001424 substituent group Chemical group 0.000 claims description 92
- 125000001072 heteroaryl group Chemical group 0.000 claims description 85
- 239000011664 nicotinic acid Substances 0.000 claims description 72
- 229960003512 nicotinic acid Drugs 0.000 claims description 72
- 229910052736 halogen Inorganic materials 0.000 claims description 70
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 70
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 66
- 239000003814 drug Substances 0.000 claims description 65
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 60
- 150000002367 halogens Chemical class 0.000 claims description 56
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 claims description 54
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 51
- 125000003118 aryl group Chemical group 0.000 claims description 45
- 206010011224 Cough Diseases 0.000 claims description 40
- RMOUBSOVHSONPZ-UHFFFAOYSA-N Isopropyl formate Chemical compound CC(C)OC=O RMOUBSOVHSONPZ-UHFFFAOYSA-N 0.000 claims description 35
- 125000001544 thienyl group Chemical group 0.000 claims description 31
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 30
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 30
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 29
- 235000001968 nicotinic acid Nutrition 0.000 claims description 27
- 229910052757 nitrogen Inorganic materials 0.000 claims description 26
- 125000002541 furyl group Chemical group 0.000 claims description 24
- GEXJFIOPGAASTP-UHFFFAOYSA-N $l^{1}-azanylethane Chemical compound CC[N] GEXJFIOPGAASTP-UHFFFAOYSA-N 0.000 claims description 23
- 125000000951 phenoxy group Chemical class [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 21
- 125000003545 alkoxy group Chemical group 0.000 claims description 19
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 19
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 18
- DIARDWDIBROFST-UHFFFAOYSA-N propan-2-yl 2-piperazin-1-ylpyridine-3-carboxylate Chemical compound CC(C)OC(=O)C1=CC=CN=C1N1CCNCC1 DIARDWDIBROFST-UHFFFAOYSA-N 0.000 claims description 17
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 15
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 15
- 239000000460 chlorine Substances 0.000 claims description 15
- 229910052760 oxygen Inorganic materials 0.000 claims description 14
- WPYMKLBDIGXBTP-UHFFFAOYSA-N Benzoic acid Natural products OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 13
- 125000004076 pyridyl group Chemical group 0.000 claims description 13
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 13
- 229910052717 sulfur Chemical group 0.000 claims description 12
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 11
- 239000001301 oxygen Chemical group 0.000 claims description 11
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 10
- 230000004044 response Effects 0.000 claims description 10
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 9
- 125000004193 piperazinyl group Chemical class 0.000 claims description 9
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 8
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 8
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 8
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 8
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 claims description 8
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 8
- 208000011341 adult acute respiratory distress syndrome Diseases 0.000 claims description 8
- 201000000028 adult respiratory distress syndrome Diseases 0.000 claims description 8
- 125000003943 azolyl group Chemical group 0.000 claims description 8
- 229910052801 chlorine Inorganic materials 0.000 claims description 8
- 239000011737 fluorine Substances 0.000 claims description 8
- 229910052731 fluorine Inorganic materials 0.000 claims description 8
- 239000011630 iodine Substances 0.000 claims description 8
- 229910052740 iodine Inorganic materials 0.000 claims description 8
- 125000003107 substituted aryl group Chemical group 0.000 claims description 8
- 239000011593 sulfur Chemical group 0.000 claims description 8
- 239000005711 Benzoic acid Substances 0.000 claims description 7
- 235000010233 benzoic acid Nutrition 0.000 claims description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 7
- 150000004702 methyl esters Chemical class 0.000 claims description 7
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 6
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 6
- 208000006673 asthma Diseases 0.000 claims description 6
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 6
- 229910052794 bromium Inorganic materials 0.000 claims description 6
- 206010006451 bronchitis Diseases 0.000 claims description 6
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 6
- 125000002950 monocyclic group Chemical group 0.000 claims description 6
- OTCNNXNYAHLHIN-CYBMUJFWSA-N propan-2-yl 2-[(3r)-3-[(2-methylpropan-2-yl)oxycarbonylamino]pyrrolidin-1-yl]pyridine-3-carboxylate Chemical compound CC(C)OC(=O)C1=CC=CN=C1N1C[C@H](NC(=O)OC(C)(C)C)CC1 OTCNNXNYAHLHIN-CYBMUJFWSA-N 0.000 claims description 6
- UQWYJBXBIWMKTO-UHFFFAOYSA-N propan-2-yl 2-[4-[(4-nitrophenyl)methyl]piperazin-1-yl]pyridine-3-carboxylate Chemical compound CC(C)OC(=O)C1=CC=CN=C1N1CCN(CC=2C=CC(=CC=2)[N+]([O-])=O)CC1 UQWYJBXBIWMKTO-UHFFFAOYSA-N 0.000 claims description 6
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 6
- 239000002671 adjuvant Substances 0.000 claims description 5
- 125000005842 heteroatom Chemical group 0.000 claims description 5
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 5
- 125000003386 piperidinyl group Chemical group 0.000 claims description 5
- MTRUSKITRXAUAY-UHFFFAOYSA-N propan-2-yl 2-[4-[(3-aminophenyl)methyl]piperazin-1-yl]pyridine-3-carboxylate Chemical compound CC(C)OC(=O)C1=CC=CN=C1N1CCN(CC=2C=C(N)C=CC=2)CC1 MTRUSKITRXAUAY-UHFFFAOYSA-N 0.000 claims description 5
- IKRGNKASNPEASH-UHFFFAOYSA-N propan-2-yl 2-[4-[(4-formylphenyl)methyl]piperazin-1-yl]pyridine-3-carboxylate Chemical compound CC(C)OC(=O)C1=CC=CN=C1N1CCN(CC=2C=CC(C=O)=CC=2)CC1 IKRGNKASNPEASH-UHFFFAOYSA-N 0.000 claims description 5
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 claims description 4
- 201000009794 Idiopathic Pulmonary Fibrosis Diseases 0.000 claims description 4
- 206010035664 Pneumonia Diseases 0.000 claims description 4
- 201000010001 Silicosis Diseases 0.000 claims description 4
- 208000010285 Ventilator-Induced Lung Injury Diseases 0.000 claims description 4
- SVDOTQXFJBTURL-GOSISDBHSA-N [2-[(3r)-3-[ethyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]pyrrolidin-1-yl]pyridin-3-yl]methyl 3,3-dimethylbutanoate Chemical compound C1[C@H](N(CC)C(=O)OC(C)(C)C)CCN1C1=NC=CC=C1COC(=O)CC(C)(C)C SVDOTQXFJBTURL-GOSISDBHSA-N 0.000 claims description 4
- 125000002619 bicyclic group Chemical group 0.000 claims description 4
- 230000001684 chronic effect Effects 0.000 claims description 4
- 208000027866 inflammatory disease Diseases 0.000 claims description 4
- 208000036971 interstitial lung disease 2 Diseases 0.000 claims description 4
- 210000004072 lung Anatomy 0.000 claims description 4
- 125000005936 piperidyl group Chemical group 0.000 claims description 4
- GXEOJKGTIKJEEU-FQLXRVMXSA-N propan-2-yl 2-[(3r)-3-[ethyl-[[4-[[ethyl-[(3r)-1-(2-methylpropanoyl)pyrrolidin-3-yl]amino]methyl]phenyl]methyl]amino]pyrrolidin-1-yl]pyridine-3-carboxylate Chemical compound C([C@H](C1)N(CC)CC2=CC=C(C=C2)CN(CC)[C@H]2CN(CC2)C(=O)C(C)C)CN1C1=NC=CC=C1C(=O)OC(C)C GXEOJKGTIKJEEU-FQLXRVMXSA-N 0.000 claims description 4
- OTCNNXNYAHLHIN-ZDUSSCGKSA-N propan-2-yl 2-[(3s)-3-[(2-methylpropan-2-yl)oxycarbonylamino]pyrrolidin-1-yl]pyridine-3-carboxylate Chemical compound CC(C)OC(=O)C1=CC=CN=C1N1C[C@@H](NC(=O)OC(C)(C)C)CC1 OTCNNXNYAHLHIN-ZDUSSCGKSA-N 0.000 claims description 4
- KIYHJMUTTDPRMD-UHFFFAOYSA-N propan-2-yl 2-[4-[(3-methoxy-4-phenylmethoxyphenyl)methyl]piperazin-1-yl]-4-phenylpyridine-3-carboxylate Chemical compound C=1C=C(OCC=2C=CC=CC=2)C(OC)=CC=1CN(CC1)CCN1C(C=1C(=O)OC(C)C)=NC=CC=1C1=CC=CC=C1 KIYHJMUTTDPRMD-UHFFFAOYSA-N 0.000 claims description 4
- MPPMTMZYPVHFAZ-UHFFFAOYSA-N propan-2-yl 2-[4-[(3-nitrophenyl)methyl]piperazin-1-yl]pyridine-3-carboxylate Chemical compound CC(C)OC(=O)C1=CC=CN=C1N1CCN(CC=2C=C(C=CC=2)[N+]([O-])=O)CC1 MPPMTMZYPVHFAZ-UHFFFAOYSA-N 0.000 claims description 4
- VWOGUHCAFQEAEK-UHFFFAOYSA-N propan-2-yl 2-[4-[(3-phenoxyphenyl)methyl]piperazin-1-yl]-4-phenylpyridine-3-carboxylate Chemical compound CC(C)OC(=O)C1=C(N2CCN(CC=3C=C(OC=4C=CC=CC=4)C=CC=3)CC2)N=CC=C1C1=CC=CC=C1 VWOGUHCAFQEAEK-UHFFFAOYSA-N 0.000 claims description 4
- QCNUTVDMWXVCJE-UHFFFAOYSA-N propan-2-yl 2-[4-[(4-aminophenyl)methyl]piperazin-1-yl]pyridine-3-carboxylate Chemical compound CC(C)OC(=O)C1=CC=CN=C1N1CCN(CC=2C=CC(N)=CC=2)CC1 QCNUTVDMWXVCJE-UHFFFAOYSA-N 0.000 claims description 4
- RKRDCCXQAQGLNW-UHFFFAOYSA-N propan-2-yl 2-[4-[[3-(4-methoxyphenoxy)phenyl]methyl]piperazin-1-yl]pyridine-3-carboxylate Chemical compound C1=CC(OC)=CC=C1OC1=CC=CC(CN2CCN(CC2)C=2C(=CC=CN=2)C(=O)OC(C)C)=C1 RKRDCCXQAQGLNW-UHFFFAOYSA-N 0.000 claims description 4
- WMGCNNNXUJMDHT-UHFFFAOYSA-N propan-2-yl 4-phenyl-2-[4-[(2-propan-2-yloxyphenyl)methyl]piperazin-1-yl]pyridine-3-carboxylate Chemical compound CC(C)OC(=O)C1=C(N2CCN(CC=3C(=CC=CC=3)OC(C)C)CC2)N=CC=C1C1=CC=CC=C1 WMGCNNNXUJMDHT-UHFFFAOYSA-N 0.000 claims description 4
- WCYMWHIPNOFARR-UHFFFAOYSA-N propan-2-yl 4-phenyl-2-[4-[(3-phenylmethoxyphenyl)methyl]piperazin-1-yl]pyridine-3-carboxylate Chemical compound CC(C)OC(=O)C1=C(N2CCN(CC=3C=C(OCC=4C=CC=CC=4)C=CC=3)CC2)N=CC=C1C1=CC=CC=C1 WCYMWHIPNOFARR-UHFFFAOYSA-N 0.000 claims description 4
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- 125000004605 1,2,3,4-tetrahydroisoquinolinyl group Chemical class C1(NCCC2=CC=CC=C12)* 0.000 claims description 3
- LMXXTTACMKHJBV-UHFFFAOYSA-N 3-[[4-(3-propan-2-yloxycarbonylpyridin-2-yl)piperazin-1-yl]methyl]benzoic acid Chemical compound CC(C)OC(=O)C1=CC=CN=C1N1CCN(CC=2C=C(C=CC=2)C(O)=O)CC1 LMXXTTACMKHJBV-UHFFFAOYSA-N 0.000 claims description 3
- YFHALRLEFFMLRP-UHFFFAOYSA-N 4-[[4-(3-propan-2-yloxycarbonylpyridin-2-yl)piperazin-1-yl]methyl]benzoic acid Chemical compound CC(C)OC(=O)C1=CC=CN=C1N1CCN(CC=2C=CC(=CC=2)C(O)=O)CC1 YFHALRLEFFMLRP-UHFFFAOYSA-N 0.000 claims description 3
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- 201000003883 Cystic fibrosis Diseases 0.000 claims description 3
- JGFBQFKZKSSODQ-UHFFFAOYSA-N Isothiocyanatocyclopropane Chemical compound S=C=NC1CC1 JGFBQFKZKSSODQ-UHFFFAOYSA-N 0.000 claims description 3
- IJGULRDALPCDDC-OAHLLOKOSA-N [2-[(3r)-3-(ethylamino)pyrrolidin-1-yl]pyridin-3-yl]methyl 3,3-dimethylbutanoate Chemical compound C1[C@H](NCC)CCN1C1=NC=CC=C1COC(=O)CC(C)(C)C IJGULRDALPCDDC-OAHLLOKOSA-N 0.000 claims description 3
- MSWDOLBRGZSHBC-QGZVFWFLSA-N [2-[(3r)-3-(ethylamino)pyrrolidin-1-yl]pyridin-3-yl]methyl benzoate Chemical compound C1[C@H](NCC)CCN1C1=NC=CC=C1COC(=O)C1=CC=CC=C1 MSWDOLBRGZSHBC-QGZVFWFLSA-N 0.000 claims description 3
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- PWLNAUNEAKQYLH-UHFFFAOYSA-N butyric acid octyl ester Natural products CCCCCCCCOC(=O)CCC PWLNAUNEAKQYLH-UHFFFAOYSA-N 0.000 claims description 3
- 125000000609 carbazolyl group Chemical class C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 claims description 3
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- 125000003983 fluorenyl group Chemical class C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- UUIQMZJEGPQKFD-UHFFFAOYSA-N n-butyric acid methyl ester Natural products CCCC(=O)OC UUIQMZJEGPQKFD-UHFFFAOYSA-N 0.000 claims description 3
- PPYLCKRAZROZIS-UHFFFAOYSA-N propan-2-yl 2-(4-benzylpiperazin-1-yl)-4-iodopyridine-3-carboxylate Chemical compound CC(C)OC(=O)C1=C(I)C=CN=C1N1CCN(CC=2C=CC=CC=2)CC1 PPYLCKRAZROZIS-UHFFFAOYSA-N 0.000 claims description 3
- OQYLDVPPEHLATQ-CQSZACIVSA-N propan-2-yl 2-[(3r)-3-[ethyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]pyrrolidin-1-yl]-4-iodopyridine-3-carboxylate Chemical compound C1[C@H](N(CC)C(=O)OC(C)(C)C)CCN1C1=NC=CC(I)=C1C(=O)OC(C)C OQYLDVPPEHLATQ-CQSZACIVSA-N 0.000 claims description 3
- UMWJMSJBMRJRSX-OAHLLOKOSA-N propan-2-yl 2-[(3r)-3-[ethyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]pyrrolidin-1-yl]pyridine-3-carboxylate Chemical compound C1[C@H](N(CC)C(=O)OC(C)(C)C)CCN1C1=NC=CC=C1C(=O)OC(C)C UMWJMSJBMRJRSX-OAHLLOKOSA-N 0.000 claims description 3
- IQGOFRMVYPJXCX-MEKGRNQZSA-N propan-2-yl 2-[(3r)-3-[ethyl-[[4-[[ethyl-[(3s)-1-(3-propan-2-yloxycarbonylpyridin-2-yl)pyrrolidin-3-yl]amino]methyl]phenyl]methyl]amino]pyrrolidin-1-yl]pyridine-3-carboxylate Chemical compound C([C@H](C1)N(CC)CC2=CC=C(C=C2)CN(CC)[C@@H]2CN(CC2)C=2C(=CC=CN=2)C(=O)OC(C)C)CN1C1=NC=CC=C1C(=O)OC(C)C IQGOFRMVYPJXCX-MEKGRNQZSA-N 0.000 claims description 3
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- IBETXKOHKDSBSP-NSHDSACASA-N propan-2-yl 2-[(3s)-3-(methylamino)pyrrolidin-1-yl]pyridine-3-carboxylate Chemical compound C1[C@@H](NC)CCN1C1=NC=CC=C1C(=O)OC(C)C IBETXKOHKDSBSP-NSHDSACASA-N 0.000 claims description 3
- IMOVIMGSLCKDOP-JTQLQIEISA-N propan-2-yl 2-[(3s)-3-aminopyrrolidin-1-yl]pyridine-3-carboxylate Chemical compound CC(C)OC(=O)C1=CC=CN=C1N1C[C@@H](N)CC1 IMOVIMGSLCKDOP-JTQLQIEISA-N 0.000 claims description 3
- OFMSXEKQYWHIAM-UHFFFAOYSA-N propan-2-yl 2-[4-[(2-bromophenyl)methyl]piperazin-1-yl]pyridine-3-carboxylate Chemical compound CC(C)OC(=O)C1=CC=CN=C1N1CCN(CC=2C(=CC=CC=2)Br)CC1 OFMSXEKQYWHIAM-UHFFFAOYSA-N 0.000 claims description 3
- LHQJKVKGIVRUHO-UHFFFAOYSA-N propan-2-yl 2-[4-[(3-benzamidophenyl)methyl]piperazin-1-yl]pyridine-3-carboxylate Chemical compound CC(C)OC(=O)C1=CC=CN=C1N1CCN(CC=2C=C(NC(=O)C=3C=CC=CC=3)C=CC=2)CC1 LHQJKVKGIVRUHO-UHFFFAOYSA-N 0.000 claims description 3
- MDHODGHIXUVVEJ-UHFFFAOYSA-N propan-2-yl 2-[4-[(3-bromophenyl)methyl]piperazin-1-yl]pyridine-3-carboxylate Chemical compound CC(C)OC(=O)C1=CC=CN=C1N1CCN(CC=2C=C(Br)C=CC=2)CC1 MDHODGHIXUVVEJ-UHFFFAOYSA-N 0.000 claims description 3
- KWTSNAQSCXNSKH-UHFFFAOYSA-N propan-2-yl 2-[4-[(4-bromophenyl)methyl]piperazin-1-yl]pyridine-3-carboxylate Chemical compound CC(C)OC(=O)C1=CC=CN=C1N1CCN(CC=2C=CC(Br)=CC=2)CC1 KWTSNAQSCXNSKH-UHFFFAOYSA-N 0.000 claims description 3
- XCYOTLRVMCKLJL-UHFFFAOYSA-N propan-2-yl 2-[4-[(4-sulfanylphenyl)methyl]piperazin-1-yl]pyridine-3-carboxylate Chemical compound CC(C)OC(=O)C1=CC=CN=C1N1CCN(CC=2C=CC(S)=CC=2)CC1 XCYOTLRVMCKLJL-UHFFFAOYSA-N 0.000 claims description 3
- HEIDSKRZLCNLNR-UHFFFAOYSA-N propan-2-yl 2-[4-[[4-(diethoxymethyl)phenyl]methyl]piperazin-1-yl]pyridine-3-carboxylate Chemical compound C1=CC(C(OCC)OCC)=CC=C1CN1CCN(C=2C(=CC=CN=2)C(=O)OC(C)C)CC1 HEIDSKRZLCNLNR-UHFFFAOYSA-N 0.000 claims description 3
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- KODYQHXVRYAXTP-NSHDSACASA-N propan-2-yl 2-[[(2s)-pyrrolidin-2-yl]methoxy]pyridine-3-carboxylate Chemical compound CC(C)OC(=O)C1=CC=CN=C1OC[C@H]1NCCC1 KODYQHXVRYAXTP-NSHDSACASA-N 0.000 claims description 3
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- WEXRFUOTKKJPNB-UHFFFAOYSA-N propan-2-yl 2-[4-[[3-[2-(trifluoromethyl)anilino]phenyl]methyl]piperazin-1-yl]pyridine-3-carboxylate Chemical compound CC(C)OC(=O)C1=CC=CN=C1N1CCN(CC=2C=C(NC=3C(=CC=CC=3)C(F)(F)F)C=CC=2)CC1 WEXRFUOTKKJPNB-UHFFFAOYSA-N 0.000 claims description 2
- GYNCYHGSKJOVBW-UHFFFAOYSA-N propan-2-yl 2-[4-[[3-[3-(trifluoromethyl)phenoxy]phenyl]methyl]piperazin-1-yl]pyridine-3-carboxylate Chemical compound CC(C)OC(=O)C1=CC=CN=C1N1CCN(CC=2C=C(OC=3C=C(C=CC=3)C(F)(F)F)C=CC=2)CC1 GYNCYHGSKJOVBW-UHFFFAOYSA-N 0.000 claims description 2
- OWRLNCORQCYHCK-UHFFFAOYSA-N propan-2-yl 2-[4-[[3-[benzoyl(methyl)amino]phenyl]methyl]piperazin-1-yl]pyridine-3-carboxylate;hydrochloride Chemical compound Cl.CC(C)OC(=O)C1=CC=CN=C1N1CCN(CC=2C=C(C=CC=2)N(C)C(=O)C=2C=CC=CC=2)CC1 OWRLNCORQCYHCK-UHFFFAOYSA-N 0.000 claims description 2
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- ZBXKPTQCAHYZGK-UHFFFAOYSA-N propan-2-yl 2-[4-[[4-(2,6-difluoroanilino)phenyl]methyl]piperazin-1-yl]pyridine-3-carboxylate Chemical compound CC(C)OC(=O)C1=CC=CN=C1N1CCN(CC=2C=CC(NC=3C(=CC=CC=3F)F)=CC=2)CC1 ZBXKPTQCAHYZGK-UHFFFAOYSA-N 0.000 claims description 2
- NOLIHEMPCZBLNU-UHFFFAOYSA-N propan-2-yl 2-[4-[[4-(2-chloroanilino)phenyl]methyl]piperazin-1-yl]pyridine-3-carboxylate Chemical compound CC(C)OC(=O)C1=CC=CN=C1N1CCN(CC=2C=CC(NC=3C(=CC=CC=3)Cl)=CC=2)CC1 NOLIHEMPCZBLNU-UHFFFAOYSA-N 0.000 claims description 2
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- CVHLHCFEIGJAAL-UHFFFAOYSA-N propan-2-yl 2-[4-[[4-(3-chlorophenoxy)phenyl]methyl]piperazin-1-yl]pyridine-3-carboxylate Chemical compound CC(C)OC(=O)C1=CC=CN=C1N1CCN(CC=2C=CC(OC=3C=C(Cl)C=CC=3)=CC=2)CC1 CVHLHCFEIGJAAL-UHFFFAOYSA-N 0.000 claims description 2
- ULNFCPYPUUTLHO-UHFFFAOYSA-N propan-2-yl 2-[4-[[4-(3-phenylpropyl)phenyl]methyl]piperazin-1-yl]pyridine-3-carboxylate;hydrochloride Chemical compound Cl.CC(C)OC(=O)C1=CC=CN=C1N1CCN(CC=2C=CC(CCCC=3C=CC=CC=3)=CC=2)CC1 ULNFCPYPUUTLHO-UHFFFAOYSA-N 0.000 claims description 2
- YQUYGVGNKUKRQA-UHFFFAOYSA-N propan-2-yl 2-[4-[[4-(4-bromophenoxy)phenyl]methyl]piperazin-1-yl]pyridine-3-carboxylate Chemical compound CC(C)OC(=O)C1=CC=CN=C1N1CCN(CC=2C=CC(OC=3C=CC(Br)=CC=3)=CC=2)CC1 YQUYGVGNKUKRQA-UHFFFAOYSA-N 0.000 claims description 2
- PGQPTOJRJRMHKS-UHFFFAOYSA-N propan-2-yl 2-[4-[[4-(4-chlorophenoxy)phenyl]methyl]piperazin-1-yl]pyridine-3-carboxylate Chemical compound CC(C)OC(=O)C1=CC=CN=C1N1CCN(CC=2C=CC(OC=3C=CC(Cl)=CC=3)=CC=2)CC1 PGQPTOJRJRMHKS-UHFFFAOYSA-N 0.000 claims description 2
- ADDGJEQOLAENEL-UHFFFAOYSA-N propan-2-yl 2-[4-[[4-(4-cyanophenoxy)phenyl]methyl]piperazin-1-yl]pyridine-3-carboxylate Chemical compound CC(C)OC(=O)C1=CC=CN=C1N1CCN(CC=2C=CC(OC=3C=CC(=CC=3)C#N)=CC=2)CC1 ADDGJEQOLAENEL-UHFFFAOYSA-N 0.000 claims description 2
- IYQIVNTUFMCDIS-UHFFFAOYSA-N propan-2-yl 2-[4-[[4-(4-fluorophenoxy)phenyl]methyl]piperazin-1-yl]-4-phenylpyridine-3-carboxylate Chemical compound CC(C)OC(=O)C1=C(N2CCN(CC=3C=CC(OC=4C=CC(F)=CC=4)=CC=3)CC2)N=CC=C1C1=CC=CC=C1 IYQIVNTUFMCDIS-UHFFFAOYSA-N 0.000 claims description 2
- NEVJSYAHCYMDLC-UHFFFAOYSA-N propan-2-yl 2-[4-[[4-(4-fluorophenoxy)phenyl]methyl]piperazin-1-yl]pyridine-3-carboxylate Chemical compound CC(C)OC(=O)C1=CC=CN=C1N1CCN(CC=2C=CC(OC=3C=CC(F)=CC=3)=CC=2)CC1 NEVJSYAHCYMDLC-UHFFFAOYSA-N 0.000 claims description 2
- QVYVUAZKGFVFIJ-UHFFFAOYSA-N propan-2-yl 2-[4-[[4-(4-methoxyanilino)phenyl]methyl]piperazin-1-yl]pyridine-3-carboxylate Chemical compound C1=CC(OC)=CC=C1NC(C=C1)=CC=C1CN1CCN(C=2C(=CC=CN=2)C(=O)OC(C)C)CC1 QVYVUAZKGFVFIJ-UHFFFAOYSA-N 0.000 claims description 2
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- URQSNZFLLDRULM-UHFFFAOYSA-N propan-2-yl 2-[4-[[4-(4-methylphenoxy)phenyl]methyl]piperazin-1-yl]pyridine-3-carboxylate Chemical compound CC(C)OC(=O)C1=CC=CN=C1N1CCN(CC=2C=CC(OC=3C=CC(C)=CC=3)=CC=2)CC1 URQSNZFLLDRULM-UHFFFAOYSA-N 0.000 claims description 2
- ZMSIZUGAWCHCJY-UHFFFAOYSA-N propan-2-yl 2-[4-[[4-(benzamidomethyl)phenyl]methyl]piperazin-1-yl]pyridine-3-carboxylate Chemical compound CC(C)OC(=O)C1=CC=CN=C1N1CCN(CC=2C=CC(CNC(=O)C=3C=CC=CC=3)=CC=2)CC1 ZMSIZUGAWCHCJY-UHFFFAOYSA-N 0.000 claims description 2
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- DRGIMGJIXDAWNO-UHFFFAOYSA-N propan-2-yl 2-[4-[[4-(ethylaminomethyl)phenyl]methyl]piperazin-1-yl]pyridine-3-carboxylate Chemical compound C1=CC(CNCC)=CC=C1CN1CCN(C=2C(=CC=CN=2)C(=O)OC(C)C)CC1 DRGIMGJIXDAWNO-UHFFFAOYSA-N 0.000 claims description 2
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- UVYXJINKYJFYKU-UHFFFAOYSA-N propan-2-yl 2-[4-[[4-[(2-chlorophenoxy)methyl]phenyl]methyl]piperazin-1-yl]pyridine-3-carboxylate Chemical compound CC(C)OC(=O)C1=CC=CN=C1N1CCN(CC=2C=CC(COC=3C(=CC=CC=3)Cl)=CC=2)CC1 UVYXJINKYJFYKU-UHFFFAOYSA-N 0.000 claims description 2
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- XQKYDWOYFBJZBR-UHFFFAOYSA-N propan-2-yl 2-[4-[[4-[(2-methylphenyl)methoxy]phenyl]methyl]piperazin-1-yl]pyridine-3-carboxylate Chemical compound CC(C)OC(=O)C1=CC=CN=C1N1CCN(CC=2C=CC(OCC=3C(=CC=CC=3)C)=CC=2)CC1 XQKYDWOYFBJZBR-UHFFFAOYSA-N 0.000 claims description 2
- RHHLWOAGTPSSKZ-UHFFFAOYSA-N propan-2-yl 2-[4-[[4-[(3-bromophenyl)methoxy]phenyl]methyl]piperazin-1-yl]pyridine-3-carboxylate Chemical compound CC(C)OC(=O)C1=CC=CN=C1N1CCN(CC=2C=CC(OCC=3C=C(Br)C=CC=3)=CC=2)CC1 RHHLWOAGTPSSKZ-UHFFFAOYSA-N 0.000 claims description 2
- GGLUTQKSNYDQSD-UHFFFAOYSA-N propan-2-yl 2-[4-[[4-[(3-chlorophenyl)methoxy]phenyl]methyl]piperazin-1-yl]pyridine-3-carboxylate Chemical compound CC(C)OC(=O)C1=CC=CN=C1N1CCN(CC=2C=CC(OCC=3C=C(Cl)C=CC=3)=CC=2)CC1 GGLUTQKSNYDQSD-UHFFFAOYSA-N 0.000 claims description 2
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- ZUQSOUHUKCRLNW-UHFFFAOYSA-N propan-2-yl 2-[4-[[4-[(3-fluorophenyl)methoxy]phenyl]methyl]piperazin-1-yl]pyridine-3-carboxylate Chemical compound CC(C)OC(=O)C1=CC=CN=C1N1CCN(CC=2C=CC(OCC=3C=C(F)C=CC=3)=CC=2)CC1 ZUQSOUHUKCRLNW-UHFFFAOYSA-N 0.000 claims description 2
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- QUMSMHIXMVIAHO-UHFFFAOYSA-N propan-2-yl 2-[4-[[4-[(4-bromophenyl)methoxy]phenyl]methyl]piperazin-1-yl]pyridine-3-carboxylate Chemical compound CC(C)OC(=O)C1=CC=CN=C1N1CCN(CC=2C=CC(OCC=3C=CC(Br)=CC=3)=CC=2)CC1 QUMSMHIXMVIAHO-UHFFFAOYSA-N 0.000 claims description 2
- ZDWMFZFBXLZURF-UHFFFAOYSA-N propan-2-yl 2-[4-[[4-[(4-chloro-2-methoxyphenyl)methoxy]phenyl]methyl]piperazin-1-yl]pyridine-3-carboxylate Chemical compound COC1=CC(Cl)=CC=C1COC(C=C1)=CC=C1CN1CCN(C=2C(=CC=CN=2)C(=O)OC(C)C)CC1 ZDWMFZFBXLZURF-UHFFFAOYSA-N 0.000 claims description 2
- ZBLNSRIIAPJPEM-UHFFFAOYSA-N propan-2-yl 2-[4-[[4-[(4-chlorophenyl)methoxy]-3-ethoxyphenyl]methyl]piperazin-1-yl]pyridine-3-carboxylate Chemical compound C=1C=C(OCC=2C=CC(Cl)=CC=2)C(OCC)=CC=1CN(CC1)CCN1C1=NC=CC=C1C(=O)OC(C)C ZBLNSRIIAPJPEM-UHFFFAOYSA-N 0.000 claims description 2
- CLROFNVAAGFQSF-UHFFFAOYSA-N propan-2-yl 2-[4-[[4-[(4-chlorophenyl)methoxy]-3-methoxyphenyl]methyl]piperazin-1-yl]pyridine-3-carboxylate Chemical compound C=1C=C(OCC=2C=CC(Cl)=CC=2)C(OC)=CC=1CN(CC1)CCN1C1=NC=CC=C1C(=O)OC(C)C CLROFNVAAGFQSF-UHFFFAOYSA-N 0.000 claims description 2
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- AMRNNEIVGVNGNA-UHFFFAOYSA-N propan-2-yl 2-[4-[[4-[(4-cyanophenyl)methoxy]phenyl]methyl]piperazin-1-yl]pyridine-3-carboxylate Chemical compound CC(C)OC(=O)C1=CC=CN=C1N1CCN(CC=2C=CC(OCC=3C=CC(=CC=3)C#N)=CC=2)CC1 AMRNNEIVGVNGNA-UHFFFAOYSA-N 0.000 claims description 2
- ZJSAQENUZYVHQC-UHFFFAOYSA-N propan-2-yl 2-[4-[[4-[(4-ethylphenyl)methoxy]phenyl]methyl]piperazin-1-yl]pyridine-3-carboxylate Chemical compound C1=CC(CC)=CC=C1COC(C=C1)=CC=C1CN1CCN(C=2C(=CC=CN=2)C(=O)OC(C)C)CC1 ZJSAQENUZYVHQC-UHFFFAOYSA-N 0.000 claims description 2
- SJASORYKFUVBEC-UHFFFAOYSA-N propan-2-yl 2-[4-[[4-[(4-fluoro-3-methoxyphenyl)methoxy]phenyl]methyl]piperazin-1-yl]pyridine-3-carboxylate Chemical compound C1=C(F)C(OC)=CC(COC=2C=CC(CN3CCN(CC3)C=3C(=CC=CN=3)C(=O)OC(C)C)=CC=2)=C1 SJASORYKFUVBEC-UHFFFAOYSA-N 0.000 claims description 2
- DLHDANBUASFLRI-UHFFFAOYSA-N propan-2-yl 2-[4-[[4-[(4-fluorophenoxy)methyl]phenyl]methyl]piperazin-1-yl]pyridine-3-carboxylate Chemical compound CC(C)OC(=O)C1=CC=CN=C1N1CCN(CC=2C=CC(COC=3C=CC(F)=CC=3)=CC=2)CC1 DLHDANBUASFLRI-UHFFFAOYSA-N 0.000 claims description 2
- PULNCBDLPWEPNQ-UHFFFAOYSA-N propan-2-yl 2-[4-[[4-[(4-fluorophenyl)methoxy]-3-methoxyphenyl]methyl]piperazin-1-yl]pyridine-3-carboxylate Chemical compound C=1C=C(OCC=2C=CC(F)=CC=2)C(OC)=CC=1CN(CC1)CCN1C1=NC=CC=C1C(=O)OC(C)C PULNCBDLPWEPNQ-UHFFFAOYSA-N 0.000 claims description 2
- UEIFZTPTFTWFIZ-UHFFFAOYSA-N propan-2-yl 2-[4-[[4-[(4-fluorophenyl)methoxy]phenyl]methyl]piperazin-1-yl]pyridine-3-carboxylate Chemical compound CC(C)OC(=O)C1=CC=CN=C1N1CCN(CC=2C=CC(OCC=3C=CC(F)=CC=3)=CC=2)CC1 UEIFZTPTFTWFIZ-UHFFFAOYSA-N 0.000 claims description 2
- XKBHEXKRTXZADP-UHFFFAOYSA-N propan-2-yl 2-[4-[[4-[(4-methylphenoxy)methyl]phenyl]methyl]piperazin-1-yl]pyridine-3-carboxylate Chemical compound CC(C)OC(=O)C1=CC=CN=C1N1CCN(CC=2C=CC(COC=3C=CC(C)=CC=3)=CC=2)CC1 XKBHEXKRTXZADP-UHFFFAOYSA-N 0.000 claims description 2
- LCLJQYHOZCHUGK-UHFFFAOYSA-N propan-2-yl 2-[4-[[4-[(4-methylphenyl)methoxy]phenyl]methyl]piperazin-1-yl]pyridine-3-carboxylate Chemical compound CC(C)OC(=O)C1=CC=CN=C1N1CCN(CC=2C=CC(OCC=3C=CC(C)=CC=3)=CC=2)CC1 LCLJQYHOZCHUGK-UHFFFAOYSA-N 0.000 claims description 2
- YCYFBQLJKJFNKC-UHFFFAOYSA-N propan-2-yl 2-[4-[[4-[(benzylamino)methyl]phenyl]methyl]piperazin-1-yl]pyridine-3-carboxylate Chemical compound CC(C)OC(=O)C1=CC=CN=C1N1CCN(CC=2C=CC(CNCC=3C=CC=CC=3)=CC=2)CC1 YCYFBQLJKJFNKC-UHFFFAOYSA-N 0.000 claims description 2
- GPIIIHBDAYYGRB-UHFFFAOYSA-N propan-2-yl 2-[4-[[4-[[benzyl(ethyl)amino]methyl]phenyl]methyl]piperazin-1-yl]pyridine-3-carboxylate Chemical compound C=1C=C(CN2CCN(CC2)C=2C(=CC=CN=2)C(=O)OC(C)C)C=CC=1CN(CC)CC1=CC=CC=C1 GPIIIHBDAYYGRB-UHFFFAOYSA-N 0.000 claims description 2
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- HNHXORUFHRZRGK-CQSZACIVSA-N propan-2-yl 2-[[(2r)-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidin-2-yl]methoxy]pyridine-3-carboxylate Chemical compound CC(C)OC(=O)C1=CC=CN=C1OC[C@@H]1N(C(=O)OC(C)(C)C)CCC1 HNHXORUFHRZRGK-CQSZACIVSA-N 0.000 description 1
- HNHXORUFHRZRGK-AWEZNQCLSA-N propan-2-yl 2-[[(2s)-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidin-2-yl]methoxy]pyridine-3-carboxylate Chemical compound CC(C)OC(=O)C1=CC=CN=C1OC[C@H]1N(C(=O)OC(C)(C)C)CCC1 HNHXORUFHRZRGK-AWEZNQCLSA-N 0.000 description 1
- SZTPTVJJKPCLPM-UHFFFAOYSA-N propan-2-yl 2-chloro-4-phenylpyridine-3-carboxylate Chemical compound CC(C)OC(=O)C1=C(Cl)N=CC=C1C1=CC=CC=C1 SZTPTVJJKPCLPM-UHFFFAOYSA-N 0.000 description 1
- STNJZGLLOVUVMN-UHFFFAOYSA-N propan-2-yl 4-formylbenzoate Chemical compound CC(C)OC(=O)C1=CC=C(C=O)C=C1 STNJZGLLOVUVMN-UHFFFAOYSA-N 0.000 description 1
- KCXFHTAICRTXLI-UHFFFAOYSA-N propane-1-sulfonic acid Chemical compound CCCS(O)(=O)=O KCXFHTAICRTXLI-UHFFFAOYSA-N 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
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- UORVCLMRJXCDCP-UHFFFAOYSA-N propynoic acid Chemical class OC(=O)C#C UORVCLMRJXCDCP-UHFFFAOYSA-N 0.000 description 1
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
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- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
- 229940107700 pyruvic acid Drugs 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
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- 230000002441 reversible effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
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- CXMXRPHRNRROMY-UHFFFAOYSA-L sebacate(2-) Chemical compound [O-]C(=O)CCCCCCCCC([O-])=O CXMXRPHRNRROMY-UHFFFAOYSA-L 0.000 description 1
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- 159000000000 sodium salts Chemical class 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
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- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
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- NBLKXSVGWHBTCD-UHFFFAOYSA-N tert-butyl 3,5-bis(bromomethyl)pyrazole-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1N=C(CBr)C=C1CBr NBLKXSVGWHBTCD-UHFFFAOYSA-N 0.000 description 1
- XTBISQIOEDXGGJ-UHFFFAOYSA-N tert-butyl 3,5-dimethylpyrazole-1-carboxylate Chemical compound CC=1C=C(C)N(C(=O)OC(C)(C)C)N=1 XTBISQIOEDXGGJ-UHFFFAOYSA-N 0.000 description 1
- RLFWFIHCWWGNPI-UHFFFAOYSA-N tert-butyl 6-[[4-(3-propan-2-yloxycarbonylpyridin-2-yl)piperazin-1-yl]methyl]-3,4-dihydro-1h-isoquinoline-2-carboxylate Chemical compound CC(C)OC(=O)C1=CC=CN=C1N1CCN(CC=2C=C3CCN(CC3=CC=2)C(=O)OC(C)(C)C)CC1 RLFWFIHCWWGNPI-UHFFFAOYSA-N 0.000 description 1
- DJCBGBZLKOFNPZ-UHFFFAOYSA-N tert-butyl 6-formyl-3,4-dihydro-1h-isoquinoline-2-carboxylate Chemical compound O=CC1=CC=C2CN(C(=O)OC(C)(C)C)CCC2=C1 DJCBGBZLKOFNPZ-UHFFFAOYSA-N 0.000 description 1
- DQQJBEAXSOOCPG-ZETCQYMHSA-N tert-butyl n-[(3s)-pyrrolidin-3-yl]carbamate Chemical compound CC(C)(C)OC(=O)N[C@H]1CCNC1 DQQJBEAXSOOCPG-ZETCQYMHSA-N 0.000 description 1
- CWXPZXBSDSIRCS-UHFFFAOYSA-N tert-butyl piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNCC1 CWXPZXBSDSIRCS-UHFFFAOYSA-N 0.000 description 1
- 125000006337 tetrafluoro ethyl group Chemical group 0.000 description 1
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
- 125000003507 tetrahydrothiofenyl group Chemical group 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 125000005247 tetrazinyl group Chemical group N1=NN=NC(=C1)* 0.000 description 1
- CFMYXEVWODSLAX-QOZOJKKESA-N tetrodotoxin Chemical compound O([C@@]([C@H]1O)(O)O[C@H]2[C@@]3(O)CO)[C@H]3[C@@H](O)[C@]11[C@H]2[C@@H](O)N=C(N)N1 CFMYXEVWODSLAX-QOZOJKKESA-N 0.000 description 1
- 229950010357 tetrodotoxin Drugs 0.000 description 1
- CFMYXEVWODSLAX-UHFFFAOYSA-N tetrodotoxin Natural products C12C(O)NC(=N)NC2(C2O)C(O)C3C(CO)(O)C1OC2(O)O3 CFMYXEVWODSLAX-UHFFFAOYSA-N 0.000 description 1
- 238000011285 therapeutic regimen Methods 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 238000003151 transfection method Methods 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- 102000035160 transmembrane proteins Human genes 0.000 description 1
- 108091005703 transmembrane proteins Proteins 0.000 description 1
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 238000004704 ultra performance liquid chromatography Methods 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 102000038650 voltage-gated calcium channel activity Human genes 0.000 description 1
- 108091023044 voltage-gated calcium channel activity Proteins 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 238000004804 winding Methods 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
- 229940071104 xylenesulfonate Drugs 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/79—Acids; Esters
- C07D213/80—Acids; Esters in position 3
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4965—Non-condensed pyrazines
- A61K31/497—Non-condensed pyrazines containing further heterocyclic rings
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P11/02—Nasal agents, e.g. decongestants
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
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- A—HUMAN NECESSITIES
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- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/08—Bronchodilators
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- A—HUMAN NECESSITIES
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- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/10—Expectorants
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/16—Central respiratory analeptics
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/72—Nitrogen atoms
- C07D213/74—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
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- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Otolaryngology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pyridine Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US29513810P | 2010-01-14 | 2010-01-14 | |
| US61/295,138 | 2010-01-14 | ||
| US31700510P | 2010-03-24 | 2010-03-24 | |
| US61/317,005 | 2010-03-24 | ||
| PCT/US2011/021114 WO2011088201A1 (en) | 2010-01-14 | 2011-01-13 | Voltage-gated sodium channel blockers |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN102802627A true CN102802627A (zh) | 2012-11-28 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2011800141112A Pending CN102802627A (zh) | 2010-01-14 | 2011-01-13 | 电压门控的钠通道阻滞剂 |
Country Status (24)
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| US (1) | US20130023541A1 (https=) |
| EP (1) | EP2523665A4 (https=) |
| JP (1) | JP2013517283A (https=) |
| KR (1) | KR20120124064A (https=) |
| CN (1) | CN102802627A (https=) |
| AR (1) | AR079906A1 (https=) |
| AU (1) | AU2011205302B2 (https=) |
| BR (1) | BR112012017266A2 (https=) |
| CA (1) | CA2787025A1 (https=) |
| CL (1) | CL2012001971A1 (https=) |
| CO (1) | CO6592051A2 (https=) |
| CR (1) | CR20120402A (https=) |
| EA (1) | EA201290644A1 (https=) |
| IL (1) | IL220836A0 (https=) |
| MA (1) | MA33987B1 (https=) |
| MX (1) | MX2012008285A (https=) |
| NZ (1) | NZ601126A (https=) |
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| ZA (1) | ZA201205126B (https=) |
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| CN109796402A (zh) * | 2018-12-28 | 2019-05-24 | 京博农化科技有限公司 | 一种烟嘧磺隆中间体2-氯-n,n-二甲基烟酰胺的制备方法 |
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- 2011-01-13 MX MX2012008285A patent/MX2012008285A/es not_active Application Discontinuation
- 2011-01-13 US US13/522,183 patent/US20130023541A1/en not_active Abandoned
- 2011-01-13 KR KR1020127021186A patent/KR20120124064A/ko not_active Withdrawn
- 2011-01-13 SG SG2012050068A patent/SG182400A1/en unknown
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2017133591A1 (zh) * | 2016-02-03 | 2017-08-10 | 上海海雁医药科技有限公司 | 杂环取代的n-磺酰基苯甲酰胺衍生物、其制法与医药上的用途 |
| US10815197B2 (en) | 2016-02-03 | 2020-10-27 | Shanghai Haiyan Pharmaceutical Technology Co., Ltd. | N-sulfonyl benzamides as voltage-gated sodium channel inhibitors |
| CN109796402A (zh) * | 2018-12-28 | 2019-05-24 | 京博农化科技有限公司 | 一种烟嘧磺隆中间体2-氯-n,n-二甲基烟酰胺的制备方法 |
| CN111548301A (zh) * | 2019-02-08 | 2020-08-18 | 三星显示有限公司 | 稠合环状化合物及包含所述稠合环状化合物的有机发光装置 |
| US11818951B2 (en) | 2019-02-08 | 2023-11-14 | Samsung Display Co., Ltd. | Condensed cyclic compound and organic light-emitting device including the same |
Also Published As
| Publication number | Publication date |
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| ZA201205126B (en) | 2013-03-27 |
| EP2523665A4 (en) | 2013-07-03 |
| KR20120124064A (ko) | 2012-11-12 |
| AU2011205302B2 (en) | 2014-10-09 |
| US20130023541A1 (en) | 2013-01-24 |
| MA33987B1 (fr) | 2013-02-01 |
| AU2011205302A1 (en) | 2012-08-02 |
| MX2012008285A (es) | 2012-08-03 |
| AR079906A1 (es) | 2012-02-29 |
| SG182400A1 (en) | 2012-08-30 |
| PE20121518A1 (es) | 2012-12-12 |
| WO2011088201A1 (en) | 2011-07-21 |
| IL220836A0 (en) | 2012-08-30 |
| PH12012501421A1 (en) | 2017-08-09 |
| JP2013517283A (ja) | 2013-05-16 |
| NZ601126A (en) | 2014-10-31 |
| EP2523665A1 (en) | 2012-11-21 |
| CA2787025A1 (en) | 2011-07-21 |
| EA201290644A1 (ru) | 2012-12-28 |
| CR20120402A (es) | 2012-09-03 |
| CL2012001971A1 (es) | 2013-01-25 |
| CO6592051A2 (es) | 2013-01-02 |
| UY33186A (https=) | 2011-07-29 |
| BR112012017266A2 (pt) | 2016-04-19 |
| TW201139406A (en) | 2011-11-16 |
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